Assessing the effectiveness of intubation as a challenge model in contagious bovine pleuropneumonia vaccine experiments

Abstract

A study was carried out to assess the effectiveness of a bronchoscope in administering a pathogenic field strain of Mycoplasma mycoides subsp. mycoides (MmmSC) in cattle challenge experiments. Out of 16 animals inoculated using the bronchoscope, 10 (62.2%) showed clinical disease as evidenced by fever and 15 (93.8%) displayed typical lesions of CBPP from which MmmSC was isolated. Serum samples collected weekly were tested by Complement Fixation Test (CFT) and competitive enzyme-linked immunosorbent assay (c-ELISA). Antibodies to MmmSC were detected in 10 out of the 16 animals by the CFT and 11 out of the 16 animals by c-ELISA. The onset of clinical disease was as early as 2 days post-inoculation, and most of the animals developed clinical disease 2 to 3 weeks post-infection. These results clearly demonstrate that nasotracheal inoculation of pathogenic strain of MmmSC with the aid of a bronchoscope can lead to early onset of clinical disease; similar to previous studies but with higher numbers of animals showing clinical disease. This is in contrast with previous studies where early clinical disease was observed in as little as 15% of inoculated animals. This nasotracheal inoculation method using a bronchoscope can, therefore, be adopted for use in experimental challenge infections of cattle. This method is found to be a better replacement to the contact transmission method whose drawback includes extra cost of donor animals and unpredictable rate and timing of transmission from intubated to challenge animals.

Models of Contagious Bovine Pleuropneumonia: Evaluation of Two Novel Strains

“…While neither modern strain produced disease as severe as the classic Gladysdale strain, the clinical results observed supported their use in that they reliably produced subacute to chronic disease. While the number of animals used was small, the results parallel previous reports as far as morbidity and the percentage of animals demonstrating clinical recovery that still had lesions at necropsy [8,26]. Mortality in our models was lower than reported from the field outbreaks.…”

“…The negative CFT results in the Ondangwa and Shawawa animals at days 24 and 42 demonstrate the unreliability of that test. The CFT is reported to detect only approximately 70% of chronic cases of CBPP and often fails to detect asymptomatic animals early in the course of infection and even some symptomatic animals [1,26,[40][41][42]. Despite direct inoculation of the organism into the lung, the CFT remained uniformly negative in all Ondangwa and Shawawa animals including those shown to have CBPP lesions and positive cultures at necropsy.…”

“…Previous models inoculated various growth media (minced lung, agar, Hayflick medium, etc.) in addition to the bacterial isolate, and bacterial numbers were variable [21,[24][25][26]. Inocula could not be quantified in models of direct contact infection.…”

Respiratory explants as a model to investigate early events of contagious bovine pleuropneumonia infection

“…In the absence of suitable laboratory animal models, the study of CBPP mainly relies on the experimental infection of cattle. This approach is very expensive, ethically debatable, and of little value for investigating the early stages of the disease [ 16 , 17 ]. Cell cultures have been used to study the host–pathogen interaction [ 9 , 13 , 18 – 20 ]; however, they do not accurately mimic the microarchitecture of the bovine airways and still foster the development of alternative, eligible in vitro models of investigation.…”

Reproduction of contagious bovine pleuropneumonia via aerosol-based challenge with Mycoplasma mycoides subsp. mycoides

“…In the absence of a meaningful small rodent model for Mmm infections, research towards improved vaccines relies on studies involving the native host. The current CBPP infection models are based on intratracheal intubation accessed via the nasal or oral cavity, applied blindly via a flexible rubber tube [3] or guided via an bronchoscope [4]. Inoculums reported were pleural effusions from CBPP-positive cattle [5], which are known to contain high concentrations of mycoplasmas [6] or broth cultures containing up to 10 10 mycoplasmas per mL [7].…”